AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for a...AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.展开更多
Accurate diagnosis of tumors needs much detailed information. However, available single imaging modality cannot provide complete or comprehensive data. Nanomedicine is the application of nanotechnology to medicine, an...Accurate diagnosis of tumors needs much detailed information. However, available single imaging modality cannot provide complete or comprehensive data. Nanomedicine is the application of nanotechnology to medicine, and multimodality imaging based on nanoparticles has been receiving extensive attention. This new hybrid imaging technology could provide complementary information from different imaging modalities using only a single injection of contrast agent. In this review, we introduce recent developments in multifunctional nanoparticles and their biomedical applications to multimodal imaging and theragnosis as nanomedicine. Most of the reviewed studies are based on the intrinsic properties of nanoparticles and their application in clinical imaging technology. The imaging techniques include positron emission tomography, single-photon emission computed tomography, computerized tomography, magnetic resonance imaging, optical imaging, and ultrasound imaging.展开更多
Background Implementing the current guidelines for leisure-time physical activity(LTPA)provides significant health benefits,especially for middle-aged adults,but it is unclear whether LTPA also translates into cardiov...Background Implementing the current guidelines for leisure-time physical activity(LTPA)provides significant health benefits,especially for middle-aged adults,but it is unclear whether LTPA also translates into cardiovascular health benefits among elderly people.Therefore,we aimed to assess the association of LTPA with the risks of cardiovascular disease(CVD),including coronary heart disease(CHD)and stroke,and all-cause mortality in an elderly population.Methods In this prospective cohort study,32,942 participants aged 60 years or older who participated in a health check-up programme in China between 2010 and 2018 were included.We evaluated the morbidity and mortality risks through the Cox regression model,competing risk model and restricted cubic spline model.Results During a median of 6.84 years of follow-up,there were 6,857 elderly people with incident CVD;a total of 6,324 deaths occurred due to all causes and 2,060 deaths occurred due to CVD.Compared with the inactive group,reductions in CVD morbidity and mortality were observed,with hazard ratios(HRs)of 0.89(95%CI:0.83–0.96)and 0.81(95%CI:0.71–0.92)in the insufficiently active group,0.86(95%CI:0.80–0.92)and 0.79(95%CI:0.69–0.90)in the sufficiently active group,and 0.79(95%CI:0.70–0.89)and 0.58(95%CI:0.45–0.76)in the highly active group,respectively;but no significant reductions were observed in the very highly active group,with HRs of 0.87(95%CI:0.71–1.06)and 0.99(95%CI:0.70–1.40),respectively.Compared with the inactive group,reductions in all-cause mortality were also observed,with a HR of 0.90(95%CI:0.84–0.97)in the insufficiently active group,0.82(95%CI:0.77–0.89)in the sufficiently active group,0.77(95%CI:0.67–0.87)in the highly active group,and 0.80(95%CI:0.64–0.98)in the very highly active group.A restricted cubic spline diagram showed that there was an L-shaped association between LTPA and the risk of all-cause mortality but a U-shaped or reverse J-shaped relationship between LTPA and the risk of CVD morbidity and mortality,especially stroke.In addition,a subgroup analysis showed that elderly population who consistently performed LTPA for ten years or more had a lower risk of morbidity and mortality.Conclusions In an elderly population,even insufficient activity is associated with a decreased risk of all-cause mortality and CVD,and moderate levels of LTPA may be optimal for CVD prevention.In addition,elderly people who consistently perform LTPA over several years may experience greater health benefits.展开更多
BACKGROUND To examine the association of baseline waist circumference(WC)and changes in WC with cardiovascular disease(CVD)and all-cause mortality among elderly people.METHODS A total of 30,041 eligible participants w...BACKGROUND To examine the association of baseline waist circumference(WC)and changes in WC with cardiovascular disease(CVD)and all-cause mortality among elderly people.METHODS A total of 30,041 eligible participants were included from a retrospective cohort in China.The same questionnaire,anthropometric and laboratory measurements were performed at baseline(2010)and the first follow-up(2013).The percent change in WC between baseline and the first follow-up was calculated to evaluate three years change of WC.We collected the occurrence of CVD and all-cause death from the first follow-up to December 31,2018.Restricted cubic splines and Cox proportionalhazards regression models were used to evaluate the relationship between baseline WC/changes in WC and mortality.RESULTS The dose-response relationships between baseline WC and CVD mortality were U-or J-shaped.In low WC group,compared with stable group,the fully adjusted hazard ratio(aHR)for CVD mortality was 1.60(95%CI:1.24−2.06)in WC gain group among men.In normal WC group,the CVD mortality risk increased with WC gain(men:aHR=1.86,95%CI:1.36−2.56;women:aHR=1.83,95%CI:1.29−2.58).In moderate-high WC group,the CVD mortality risk increased with WC gain(men:aHR=1.76,95%CI:1.08−2.88;women:aHR=1.46,95%CI:1.04−2.05)and risk decreased with WC loss(men:aHR=0.54,95%CI:0.30−0.98;women:aHR=0.59,95%CI:0.37−0.96).CONCLUSIONS For the elderly population,WC gain may increase CVD mortality risk regardless of baseline WC,whereas WC reduction could decrease the risk only in the moderate-high WC group.展开更多
Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology,and immune checkpoint inhibitors have successfully achieved responses in numbe...Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology,and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types,including hematopoietic malignancy.However,acute myeloid leukemia(AML)is a heterogeneous disease and there is stll a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage.展开更多
基金Supported by the National Natural Science Foundation of China(No.82071888)the Natural Science Foundation of Shandong Province(No.ZR2021MH351,No.ZR2020MH074)+1 种基金the Introduction and Cultivation Project for Young Innovative Talents in Shandong ProvinceWeifang Science and Technology Development Plan(No.2021GX057).
文摘AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.
文摘Accurate diagnosis of tumors needs much detailed information. However, available single imaging modality cannot provide complete or comprehensive data. Nanomedicine is the application of nanotechnology to medicine, and multimodality imaging based on nanoparticles has been receiving extensive attention. This new hybrid imaging technology could provide complementary information from different imaging modalities using only a single injection of contrast agent. In this review, we introduce recent developments in multifunctional nanoparticles and their biomedical applications to multimodal imaging and theragnosis as nanomedicine. Most of the reviewed studies are based on the intrinsic properties of nanoparticles and their application in clinical imaging technology. The imaging techniques include positron emission tomography, single-photon emission computed tomography, computerized tomography, magnetic resonance imaging, optical imaging, and ultrasound imaging.
基金supported by National Key Research and Development Programme of China(2017YFC1307705&2016YFC0106907)the Science and Technology Development Programme of Henan(No.201403007)。
文摘Background Implementing the current guidelines for leisure-time physical activity(LTPA)provides significant health benefits,especially for middle-aged adults,but it is unclear whether LTPA also translates into cardiovascular health benefits among elderly people.Therefore,we aimed to assess the association of LTPA with the risks of cardiovascular disease(CVD),including coronary heart disease(CHD)and stroke,and all-cause mortality in an elderly population.Methods In this prospective cohort study,32,942 participants aged 60 years or older who participated in a health check-up programme in China between 2010 and 2018 were included.We evaluated the morbidity and mortality risks through the Cox regression model,competing risk model and restricted cubic spline model.Results During a median of 6.84 years of follow-up,there were 6,857 elderly people with incident CVD;a total of 6,324 deaths occurred due to all causes and 2,060 deaths occurred due to CVD.Compared with the inactive group,reductions in CVD morbidity and mortality were observed,with hazard ratios(HRs)of 0.89(95%CI:0.83–0.96)and 0.81(95%CI:0.71–0.92)in the insufficiently active group,0.86(95%CI:0.80–0.92)and 0.79(95%CI:0.69–0.90)in the sufficiently active group,and 0.79(95%CI:0.70–0.89)and 0.58(95%CI:0.45–0.76)in the highly active group,respectively;but no significant reductions were observed in the very highly active group,with HRs of 0.87(95%CI:0.71–1.06)and 0.99(95%CI:0.70–1.40),respectively.Compared with the inactive group,reductions in all-cause mortality were also observed,with a HR of 0.90(95%CI:0.84–0.97)in the insufficiently active group,0.82(95%CI:0.77–0.89)in the sufficiently active group,0.77(95%CI:0.67–0.87)in the highly active group,and 0.80(95%CI:0.64–0.98)in the very highly active group.A restricted cubic spline diagram showed that there was an L-shaped association between LTPA and the risk of all-cause mortality but a U-shaped or reverse J-shaped relationship between LTPA and the risk of CVD morbidity and mortality,especially stroke.In addition,a subgroup analysis showed that elderly population who consistently performed LTPA for ten years or more had a lower risk of morbidity and mortality.Conclusions In an elderly population,even insufficient activity is associated with a decreased risk of all-cause mortality and CVD,and moderate levels of LTPA may be optimal for CVD prevention.In addition,elderly people who consistently perform LTPA over several years may experience greater health benefits.
基金supported by the National Key Research and Development Programme of China(2017YFC1307705&2016YFC0106907)the Science and Technology Development Programme of Henan(No.201403007).
文摘BACKGROUND To examine the association of baseline waist circumference(WC)and changes in WC with cardiovascular disease(CVD)and all-cause mortality among elderly people.METHODS A total of 30,041 eligible participants were included from a retrospective cohort in China.The same questionnaire,anthropometric and laboratory measurements were performed at baseline(2010)and the first follow-up(2013).The percent change in WC between baseline and the first follow-up was calculated to evaluate three years change of WC.We collected the occurrence of CVD and all-cause death from the first follow-up to December 31,2018.Restricted cubic splines and Cox proportionalhazards regression models were used to evaluate the relationship between baseline WC/changes in WC and mortality.RESULTS The dose-response relationships between baseline WC and CVD mortality were U-or J-shaped.In low WC group,compared with stable group,the fully adjusted hazard ratio(aHR)for CVD mortality was 1.60(95%CI:1.24−2.06)in WC gain group among men.In normal WC group,the CVD mortality risk increased with WC gain(men:aHR=1.86,95%CI:1.36−2.56;women:aHR=1.83,95%CI:1.29−2.58).In moderate-high WC group,the CVD mortality risk increased with WC gain(men:aHR=1.76,95%CI:1.08−2.88;women:aHR=1.46,95%CI:1.04−2.05)and risk decreased with WC loss(men:aHR=0.54,95%CI:0.30−0.98;women:aHR=0.59,95%CI:0.37−0.96).CONCLUSIONS For the elderly population,WC gain may increase CVD mortality risk regardless of baseline WC,whereas WC reduction could decrease the risk only in the moderate-high WC group.
基金This study was supported by Training Project for National Natural Science Foundation from The Third Affliated Hospital of Sun Yat-sen University(No.2022GZRPYMS05 to Zi-Jie Long)Science and Technology Planning Project of Guangzhou(No.202201020400 to Zi-Jie Long).
文摘Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology,and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types,including hematopoietic malignancy.However,acute myeloid leukemia(AML)is a heterogeneous disease and there is stll a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage.
